Despite preclinical data strongly supported a potential role of HER3 signaling in acquired resistance to HER1 inhibitors [56], two randomized phase II study in HNSCC [53] and metastatic colorectal cancers [57] showed no benefits of the dual inhibition of HER1 and HER3 with duligotuzumab as compared to inhibition of HER1 alone with cetuximab. Here, EGFR is linked to head and neck squamous cell carcinoma.